All information about the visual world is conveyed from the eyes to the visual centers of the brain by retinal ganglion cells (RGCs). The overall objective of the proposed research program is to further our understanding of the functional organization of these neurons using the mouse retina as a model system. The potential advantage of this approach is the possibility of using the tools of molecular biology to engineer animals (commonly referred to as knockouts) which lack specific cellular attributes. Before taking advantage of the knockout technology, it is essential to obtain information about the organizational properties of RGCs in the normal mouse. For this purpose, we will make patch-clamp recordings in conjunction with Lucifer yellow filling of RGCs to document the structural and functional properties of wild-type mouse RGCs. As the first specific aim, we will assess the visual receptive field properties of these neurons using an isolated retinal whole mount preparation in order to determine how the morphologically defined RGC classes correlate with their salient responses to light. This will provide the first structural/functional information about RGCs in the mouse retina. Specific aim 2 will document the intrinsic membrane properties of the different classes of RGCs to test the hypothesis that they express different excitable membrane properties. Our preliminary results indicate that only alpha-type cells manifest T-type currents that regulate bursting activity. Specific aim 3 will assess the functional properties of RGCs in knockouts lacking nitric oxide (NO), a gas that been suggested to act as a retinal neurotransmitter. As yet, however, little is known about the involvement of NO in the functional organization of the mammalian retina. In the ferret, I have found that increasing NO selectively blocks "Off" responses in retinal ganglion cells, so it will be particularly interesting to assess whether or not On and Off channels are differentially modified in these genetically altered mice. NO has also been implicated in the refinement of early projection patterns in the developing CNS. Specific aim 4 will determine whether this gas acts to regulate the structural properties of ganglion cells. In particular, we will test the hypothesis that NO is required for the normal stratification of ganglion cell dendrites into On and Off sublaminae of the IPL.